This disclosure relates to the field of orally disintegrating tablet containing microparticles with flexible release patterns and taste masking.
Multiparticulates are well known pharmaceutical dosage forms that can be utilized for a wide range of applications. When taken orally, multiparticulates generally disperse freely in the gastrointestinal (GI) tract, maximize absorption, and minimize side effects. See, for example, Multiparticulate Oral Drug Delivery (Marcel Dekker, 1994), and Pharmaceutical Pelletization Technology (Marcel Dekker, 1989).
Oral multiparticulate technology, in the form of beads, mini-tablets and microspheres with coated and/or matrix architecture, offers a wide range of drug release profile flexibility for single or multiple drug combinations. They can be formulated as modified-release (e.g., extended, delayed, pulsed), immediate-release, bioavailability-enhanced, or taste-masked dosage forms.
Extended release (ER) formulations provide several advantages, including, but not limited to, increased patient compliance, reduced dose frequency, and reduced side-effect profile. However, the potential therapeutic advantages of once daily extended release dosage forms with extended duration of release may be compromised by poor or unpredictable drug absorption from the colon. The rate and extent of absorption may be influence by the colon's physiological factors, such as less volume, highly viscous fluid, which thereby diminishes drug absorption. Multiparticulates provide predictable and consistent gastrointestinal transit and lower chances of undesirable events (e.g., dose dumping, colonic streaming) associated with single-unit dosage forms such as tablets. These multiparticulates can be dosed within capsules, tablets (microspheres, coated beads) or sachets. One application for multiparticulates is for delivery of drugs for which rapid delivery of the drug is desired for rapid onset of action. Such formulations must rapidly release the drug to the GI tract. For example, multiparticulates may be incorporated into orally disintegrating tablets (ODTs) that rapidly release the drug when the dosage form is placed into the mouth.
In such formulations, when the drug has an unpleasant taste it is often desirable to delay the release of the drug until the multiparticulate has exited the mouth to improve patient compliance. In order to provide taste masking, the materials used to form the multiparticulates must be capable of satisfying two competing constraints. On the one hand, the materials need to be sufficiently robust so as to remain intact and provide taste masking in the mouth. On the other hand, the materials used to provide taste masking should be capable of quickly releasing the drug once the multiparticulate has exited the mouth. If the materials that provide taste masking are too robust, then the materials may undesirably inhibit or slow the release of the drug in the GI tract. In addition, taste masked multiparticulates are fine enough to prevent grittiness in the mouth.
However, it is known to be difficult to coat fine particles (d50 less than 200 microns) uniformly for taste masking, extended release or modified release applications. One problem is due to attrition of the particles during fluid bed coating. Another problem is that granules and multiparticulates can often present a gritty sensation in the patient's mouth. A further problem is that due to electrostatic charge interactions during manufacturing, microparticles are prone to agglomeration prior to coating. It is desired that a dosage form provide a pleasing feel in the mouth.
There is therefore a need to develop fine particle suitable for modified release and/or taste masked orally disintegrating dosage forms that improve patient compliance, target drug release at specific site of absorption, maximize colonic absorption, reduce peak-to-trough variations, and maintain plasma levels within therapeutic ranges.